Circulating DNA methylation level of CXCR5 correlates with inflammation in patients with Rheumatoid Arthritis

To assess the correlation of cg04537602 circulating methylation levels of CXCR5 with clinical characteristics in patients with rheumatoid arthritis (RA) and differential methylation between RA and osteoarthritis(OA) as well as normal individuals.Methods Peripheral blood samples were collected from 241 RA patients, 30 patients with OA and 30 healthy controls (HC). Target region methylation sequencing to the promoter region of CXCR5 was achieved using MethylTarget. The methylation level of cg04537602 and methylation haplotype were compared among the three groups, and the correlation between methylation levels and clinical characteristics of RA patients was performed by Spearman's rank correlation analysis.Results Peripheral blood DNA methylation levels were significantly increased in cg04537602 compared to OA patients and HC . Rheumatoid factor (RF) combined with cyclic citrullinated peptide (CCP) and CXCR5 methylation levels have improved accuracy in predicting RA.The methylation level of cg04537602 in RA was positively correlated with C-reactive protein. We also observed a significant increase in hypermethylation haplotype in RA patients compared with OA patients and HC, which was consistent with single-loci-based CpG methylation measurement.Conclusion Circulating DNA methylation level of CXCR5 is correlated with inflammation and disease activity in RA patients and shows significant power to identify RA from OA and healthy individuals. Our results indicate the potential role of CXCR5 circulating DNA methylation in patient management and precision medicine in RA.